IL-12和IL-6与实验性急性坏死性胰腺炎严重程度的关系
赖铭裕,广西医科大学第一附属医院老年消化内科 广西壮族自治区南宁市 530021
梁志海,孙学成,广西医科大学 广西壮族自治区南宁市 530021
唐国都,邓德海,广西医科大学第一附属医院消化内科 广西壮族自治区南宁市 530021
赖铭裕,男,1969-07生, 广西合浦人, 广西医科大学消化内科硕士,从事消化内科临床工作.
广西自然科学基金资助项目(桂科自),No.0447054
通讯作者:唐国都,530021, 广西壮族自治区南宁市双拥路6号,广西医科大学第一附属医院消化内科. tguodu02@yahoo.com.cn
, http://www.100md.com
电话: 0771-5356501
收稿日期:2005-03-14 接受日期:2005-04-01
Correlation of interleukin-12 and interleukin-6with severity of experimental acute necrotizing pancreatitis
Ming-Yu Lai, Zhi-HaiLiang, Guo-Du Tang, Xue-Cheng Sun, De-Hai Deng
Ming-Yu Lai, Department of Gerontism Gastroenterology, the FirstAffiliated Hospital of Guangxi Medical University, Nanning 530021, GuangxiProvince, China.
, 百拇医药
Zhi-Hai Liang, Xue-Cheng Sun, Graduates of Guangxi MedicalUniversity, Nanning 530021, Guangxi Province, China
Guo-Du Tang, De-Hai Deng, Department of Gastroenterology, the FirstAffiliated Hospital of Guangxi Medical University, Nanning 530021, GuangxiProvince, China
Correspondence to: Guo-Du Tang, Department of Gastroenterology, theFirst Affiliated Hospital of Guangxi Medical University, Nanning 530021,Guangxi Province, China. tguodu02@yahoo.com.cn
, http://www.100md.com
Received: 2005-03-14 Accepted:2005-04-01
Abstract
AIM: To investigate the change of serum interleukin-12 (IL-12) andinterleukin-6 (IL-6) concentrations and the correlation with the severityof pancreas damages in experimental acute necrotizing pancreatitis (ANP).
METHODS: Ninety-two Spraque-Dawley rats were randomly divided intoANP (group A, n = 36), IL-10-interfering (group I, n = 32)and control group (group C, n = 24). Rats in group A and I wereinjected intraperitoneally with 6% L-Arginine (3×1.0mg/g) three times at an interval of 1 hour to induce ANP and those ingroup C received saline intraperitoneal injection only. Rats in Group Iwere treated with recombinment human IL-10 at 2th,5thand 8thhour (10 000 U for each time) after the L-arginine injection. Rats werekilled at 4th,12th,24thand 36thhour after the last L-arginine injection. The pathological characteristicsof the pancreas observed under light microscope. Serum amylase, IL-12 andIL-6 concentrations were detected by substrate-enzyme technique and ELISArespectively.
, 百拇医药
RESULTS: The pathological scores of pancreas, the concentrations ofserum amylase, IL-12 and IL-6 in rats of group A were markedly higher thangroup C (24 h, serum amylase: 3 264.89±1627.18 vs 364.61±64.24,P<0.01; IL-12: 104.68±23.93vs 56.72±22.67pg/L, P<0.01; IL-6: 132.95±26.64vs 81.90±9.93pg/L, P<0.01). After administration of IL-10, the pathologicalscores of pancreas, the concentrations of serum amylase, IL-12 and IL-6 inwere significantly decreased in group I as compared with those in group A(24 h, pathological scores: 4.75±1.75vs 7.89±1.17,P<0.01; serum amylase: 1 481.13±336.48vs 3 264.89±1627.18, P<0.01; IL-12: 81.31±17.23vs 104.68±23.93pg/L, P<0.05; IL-6: 96.80±18.28vs 132.95±26.64pg/L, P<0.01). The concentration of IL-12 was positivelycorrelated with pathological scores of pancreas (r = 0.603, P<0.001)and serum amylase concentration (r = 0.323, P<0.05), buthad no marked relations with IL-6 concentration (P>0.05).
, 百拇医药
CONCLUSION: The serum concentrations of IL-12 and IL-6 are markedlyelevated in experimental ANP. The pancreatic damages are improved afterIL-10 administration. Serum IL-12 is positively related to the severity ofpancreatic damages.
Key Words: Interleukin-12; Inteleukin-6; Acute necrotizingpancreatitis
Lai MY, Liang ZH, Tang GD, Sun XC, Deng DH. Correlation of interleukin-12and interleukin-6 with severity of experimental acute necrotizingpancreatitis. Shijie Huaren Xiaohua Zazhi 2005;13(13):1550-1553
, http://www.100md.com
摘要目的:探讨血清白介素12(IL-12)浓度在急性坏死性胰腺炎(ANP)中的变化以及他与胰腺病变严重程度的关系.
方法:SD大鼠92只随机分为3组，胰腺炎组(A组，n= 36)和干预组(I组，n =32)大鼠都分3次60 g/L左旋精氨酸(L-arginine)ip建立ANP大鼠模型;I组在诱导胰腺炎后2，5，8h分3次ip IL-10各10 000 U.正常对照组(C组，n =24)接受同剂量的生理盐水.于4，12，24，36 h分批处死大鼠，光镜下观察胰腺组织并进行病理评分，用酶底物法检测血清淀粉酶，用ELISA法检测IL-12和 IL-6浓度.
结果: A组胰腺病理评分、血清淀粉酶、IL-12及IL-6的水平显著高于对照组(24h, 血清淀粉酶:3 264.89±1627.18 vs 364.61±64.24,P<0.01; IL-12: 104.68±23.93vs 56.72±22.67pg/L, P<0.01; IL-6: 132.95±26.64 vs 81.90±9.93 pg/L, P<0.01)，I组可使各观察指标较A组明显下降(24h, 病理评分: 4.75±1.75 vs 7.89±1.17, P<0.01;血清淀粉酶: 1481.13±336.48 vs 3264.89±1 627.18, P<0.01;IL-12: 81.31±17.23vs 104.68±23.93pg/L, P<0.05; IL-6: 96.80±18.28vs 132.95±26.64pg/L, P<0.01);IL-12与病理评分(r= 0.603, P<0.001)及血清淀粉酶水平(r= 0.323, P<0.05)存在正相关，但是与IL-6无显著相关性(P>0.05).
, http://www.100md.com
结论:大剂量L-arginine ip诱导的ANP大鼠中，血清IL-12及IL-6显著上升，应用IL-10可减轻胰腺病变程度，IL-12浓度与胰腺病变正相关.
关键词:白介素12; 白介素6; 急性坏死性胰腺炎
赖铭裕,梁志海,唐国都, 孙学成, 邓德海.IL-12和IL-6与实验性急性坏死性胰腺炎严重程度的关系.世界华人消化杂志 2005;13(13):1550-1553
Raraty MG, Connor S, Criddle DN, Sutton R, Neoptolemos JP. Acutepancreatitis and organ failure:pathophysiology,natural history, and management strategies.Curr Gastroenterol Rep 2004;6:99-103
, http://www.100md.com
2 杨家和, 钱其军, 吴孟超,郭亚军. 白介素12:重要的免疫调节因子.世界华人消化杂志 1999;7:71-72
3 Bhatia M. Novel therapeutic targets for acute pancreatitis andassociated multiple organ dysfunction syndrome.
CurrDrug Targets Inflamm Allergy 2002;1:343-351
4 尚宏清, 李非,张再兴,孙家邦.分次大剂量L-精氨酸腹腔内注射致大鼠急性坏死性胰腺炎模型的研究.
首都医科大学学报 2000;21:322-324
5 谭至柔, 唐国都,姜海行, 邓德海, 袁海锋.抗氧化剂对急性胰腺炎大鼠核因子-kB和一氧分氮合酶的影响.
, http://www.100md.com
世界华人消化杂志 2004;12:711-713
6 Kusske AM, Rongione AJ, Ashley SW, McFadden DW, Reber HA.Interleukin-10 prevents death in lethal necrotizing
pacreatitisin mice. Surgery 1996;120:284-288
7 Leser HG, Gross V, Scheibenbogen C, Heinisch A, Salm R, Lausen M,Ruckauer K, Andreesen R, Farthmann EH,ScholmerichJ. Elevation of serum interleukin-6 concentration precedes acute-phaseresponse and reflects severity in
, http://www.100md.com
acutepancreatitis. Gastroenterology 1991;101:782-785
8 Jiang CF, Shiau YC, Ng KW, Tan SW. Serum interleukin-6, tumornecrosis factor alpha and C-reactive protein in
earlyprediction of severity of acute pancreatitis. J Chin Med Assoc 2004;67:442-446
9 王昌成, 马兴刚, 徐淮,朱九成, 王建营, 陈刚英.血清IL-6、IL-8和TNF-a在早期诊断重症急性胰腺炎中的价值.
中华急诊医学杂志 2001;10:252-253
, 百拇医药
10 王健, 易继林. 白介素-10治疗急性胰腺炎的实验研究.中国危重病急救医学 2002;14:371-374
11 Warzecha Z, Dembinski A, Ceranowicz P, Konturek SJ, Tomaszewska R,Stachura J, Konturek PC. IGF-1
stimulates production ofinterleukin-10 and inhibits development of caerulein-induced pancreatitis.
Physiol Pharmacol 2003;54:575-590
12 Chen ZQ, Tang YQ, Zhang Y, Jiang ZH, Mao EQ, Zou WG, Lei RQ, Han TQ,Zhang SD. Adenoviral transfer of human
, 百拇医药
interleukin-10 gene in lethalpancreatitis. World J Gastroenterol 2004;10:3021-3025
13 Sweeney KJ, Kell MR, Coates C, Murphy T, Reynolds JV. Serum antigen(s) drive the proinflammatory T cell
response in acute pancreatitis. BrJ Surg 2003;90:313-319
14 Uehara S, Gothoh K, Handa H, Tomita H, Tomita Y. Immune function inpatients with acute pancreatitis.
J Gastroenterol Hepatol 2003;18:363-370
, http://www.100md.com
15 张群华, 蔡端,吴树强,姜永峰,候兰娣, 张延龄. 急性坏死性胰腺炎大鼠的炎性递质变化和生长抑素的作用.
中华医学杂志 1997;77:355-358
16 Pezzilli R, Miniero R, Cappelletti O, Barakat B. Behavior of seruminterleukin 12 in human acute pancreatitis.
Pancreas 1999;18:247-251
17 艾迎春, 韩桂华, 郭公新,陈福军. IL -8和IL-12与急性胰腺炎分类的探讨.黑龙江医药科学 2004;27:34-35
18 姚婷, 王书奎, 陈军,姚堃, 秦浚川, 季晓辉.M-CSF、IL-10对单核细胞IL-12、IL-18产生及HLA-DR和CD80表达的影响.
细胞与分子免疫学杂志 2004;20:67-69
编辑 潘伯荣 审读 张海宁, 百拇医药( 赖铭裕, 梁志海, 唐国都, 孙学成, 邓德海)
梁志海,孙学成,广西医科大学 广西壮族自治区南宁市 530021
唐国都,邓德海,广西医科大学第一附属医院消化内科 广西壮族自治区南宁市 530021
赖铭裕,男,1969-07生, 广西合浦人, 广西医科大学消化内科硕士,从事消化内科临床工作.
广西自然科学基金资助项目(桂科自),No.0447054
通讯作者:唐国都,530021, 广西壮族自治区南宁市双拥路6号,广西医科大学第一附属医院消化内科. tguodu02@yahoo.com.cn
, http://www.100md.com
电话: 0771-5356501
收稿日期:2005-03-14 接受日期:2005-04-01
Correlation of interleukin-12 and interleukin-6with severity of experimental acute necrotizing pancreatitis
Ming-Yu Lai, Zhi-HaiLiang, Guo-Du Tang, Xue-Cheng Sun, De-Hai Deng
Ming-Yu Lai, Department of Gerontism Gastroenterology, the FirstAffiliated Hospital of Guangxi Medical University, Nanning 530021, GuangxiProvince, China.
, 百拇医药
Zhi-Hai Liang, Xue-Cheng Sun, Graduates of Guangxi MedicalUniversity, Nanning 530021, Guangxi Province, China
Guo-Du Tang, De-Hai Deng, Department of Gastroenterology, the FirstAffiliated Hospital of Guangxi Medical University, Nanning 530021, GuangxiProvince, China
Correspondence to: Guo-Du Tang, Department of Gastroenterology, theFirst Affiliated Hospital of Guangxi Medical University, Nanning 530021,Guangxi Province, China. tguodu02@yahoo.com.cn
, http://www.100md.com
Received: 2005-03-14 Accepted:2005-04-01
Abstract
AIM: To investigate the change of serum interleukin-12 (IL-12) andinterleukin-6 (IL-6) concentrations and the correlation with the severityof pancreas damages in experimental acute necrotizing pancreatitis (ANP).
METHODS: Ninety-two Spraque-Dawley rats were randomly divided intoANP (group A, n = 36), IL-10-interfering (group I, n = 32)and control group (group C, n = 24). Rats in group A and I wereinjected intraperitoneally with 6% L-Arginine (3×1.0mg/g) three times at an interval of 1 hour to induce ANP and those ingroup C received saline intraperitoneal injection only. Rats in Group Iwere treated with recombinment human IL-10 at 2th,5thand 8thhour (10 000 U for each time) after the L-arginine injection. Rats werekilled at 4th,12th,24thand 36thhour after the last L-arginine injection. The pathological characteristicsof the pancreas observed under light microscope. Serum amylase, IL-12 andIL-6 concentrations were detected by substrate-enzyme technique and ELISArespectively.
, 百拇医药
RESULTS: The pathological scores of pancreas, the concentrations ofserum amylase, IL-12 and IL-6 in rats of group A were markedly higher thangroup C (24 h, serum amylase: 3 264.89±1627.18 vs 364.61±64.24,P<0.01; IL-12: 104.68±23.93vs 56.72±22.67pg/L, P<0.01; IL-6: 132.95±26.64vs 81.90±9.93pg/L, P<0.01). After administration of IL-10, the pathologicalscores of pancreas, the concentrations of serum amylase, IL-12 and IL-6 inwere significantly decreased in group I as compared with those in group A(24 h, pathological scores: 4.75±1.75vs 7.89±1.17,P<0.01; serum amylase: 1 481.13±336.48vs 3 264.89±1627.18, P<0.01; IL-12: 81.31±17.23vs 104.68±23.93pg/L, P<0.05; IL-6: 96.80±18.28vs 132.95±26.64pg/L, P<0.01). The concentration of IL-12 was positivelycorrelated with pathological scores of pancreas (r = 0.603, P<0.001)and serum amylase concentration (r = 0.323, P<0.05), buthad no marked relations with IL-6 concentration (P>0.05).
, 百拇医药
CONCLUSION: The serum concentrations of IL-12 and IL-6 are markedlyelevated in experimental ANP. The pancreatic damages are improved afterIL-10 administration. Serum IL-12 is positively related to the severity ofpancreatic damages.
Key Words: Interleukin-12; Inteleukin-6; Acute necrotizingpancreatitis
Lai MY, Liang ZH, Tang GD, Sun XC, Deng DH. Correlation of interleukin-12and interleukin-6 with severity of experimental acute necrotizingpancreatitis. Shijie Huaren Xiaohua Zazhi 2005;13(13):1550-1553
, http://www.100md.com
摘要目的:探讨血清白介素12(IL-12)浓度在急性坏死性胰腺炎(ANP)中的变化以及他与胰腺病变严重程度的关系.
方法:SD大鼠92只随机分为3组，胰腺炎组(A组，n= 36)和干预组(I组，n =32)大鼠都分3次60 g/L左旋精氨酸(L-arginine)ip建立ANP大鼠模型;I组在诱导胰腺炎后2，5，8h分3次ip IL-10各10 000 U.正常对照组(C组，n =24)接受同剂量的生理盐水.于4，12，24，36 h分批处死大鼠，光镜下观察胰腺组织并进行病理评分，用酶底物法检测血清淀粉酶，用ELISA法检测IL-12和 IL-6浓度.
结果: A组胰腺病理评分、血清淀粉酶、IL-12及IL-6的水平显著高于对照组(24h, 血清淀粉酶:3 264.89±1627.18 vs 364.61±64.24,P<0.01; IL-12: 104.68±23.93vs 56.72±22.67pg/L, P<0.01; IL-6: 132.95±26.64 vs 81.90±9.93 pg/L, P<0.01)，I组可使各观察指标较A组明显下降(24h, 病理评分: 4.75±1.75 vs 7.89±1.17, P<0.01;血清淀粉酶: 1481.13±336.48 vs 3264.89±1 627.18, P<0.01;IL-12: 81.31±17.23vs 104.68±23.93pg/L, P<0.05; IL-6: 96.80±18.28vs 132.95±26.64pg/L, P<0.01);IL-12与病理评分(r= 0.603, P<0.001)及血清淀粉酶水平(r= 0.323, P<0.05)存在正相关，但是与IL-6无显著相关性(P>0.05).
, http://www.100md.com
结论:大剂量L-arginine ip诱导的ANP大鼠中，血清IL-12及IL-6显著上升，应用IL-10可减轻胰腺病变程度，IL-12浓度与胰腺病变正相关.
关键词:白介素12; 白介素6; 急性坏死性胰腺炎
赖铭裕,梁志海,唐国都, 孙学成, 邓德海.IL-12和IL-6与实验性急性坏死性胰腺炎严重程度的关系.世界华人消化杂志 2005;13(13):1550-1553
Raraty MG, Connor S, Criddle DN, Sutton R, Neoptolemos JP. Acutepancreatitis and organ failure:pathophysiology,natural history, and management strategies.Curr Gastroenterol Rep 2004;6:99-103
, http://www.100md.com
2 杨家和, 钱其军, 吴孟超,郭亚军. 白介素12:重要的免疫调节因子.世界华人消化杂志 1999;7:71-72
3 Bhatia M. Novel therapeutic targets for acute pancreatitis andassociated multiple organ dysfunction syndrome.
CurrDrug Targets Inflamm Allergy 2002;1:343-351
4 尚宏清, 李非,张再兴,孙家邦.分次大剂量L-精氨酸腹腔内注射致大鼠急性坏死性胰腺炎模型的研究.
首都医科大学学报 2000;21:322-324
5 谭至柔, 唐国都,姜海行, 邓德海, 袁海锋.抗氧化剂对急性胰腺炎大鼠核因子-kB和一氧分氮合酶的影响.
, http://www.100md.com
世界华人消化杂志 2004;12:711-713
6 Kusske AM, Rongione AJ, Ashley SW, McFadden DW, Reber HA.Interleukin-10 prevents death in lethal necrotizing
pacreatitisin mice. Surgery 1996;120:284-288
7 Leser HG, Gross V, Scheibenbogen C, Heinisch A, Salm R, Lausen M,Ruckauer K, Andreesen R, Farthmann EH,ScholmerichJ. Elevation of serum interleukin-6 concentration precedes acute-phaseresponse and reflects severity in
, http://www.100md.com
acutepancreatitis. Gastroenterology 1991;101:782-785
8 Jiang CF, Shiau YC, Ng KW, Tan SW. Serum interleukin-6, tumornecrosis factor alpha and C-reactive protein in
earlyprediction of severity of acute pancreatitis. J Chin Med Assoc 2004;67:442-446
9 王昌成, 马兴刚, 徐淮,朱九成, 王建营, 陈刚英.血清IL-6、IL-8和TNF-a在早期诊断重症急性胰腺炎中的价值.
中华急诊医学杂志 2001;10:252-253
, 百拇医药
10 王健, 易继林. 白介素-10治疗急性胰腺炎的实验研究.中国危重病急救医学 2002;14:371-374
11 Warzecha Z, Dembinski A, Ceranowicz P, Konturek SJ, Tomaszewska R,Stachura J, Konturek PC. IGF-1
stimulates production ofinterleukin-10 and inhibits development of caerulein-induced pancreatitis.
Physiol Pharmacol 2003;54:575-590
12 Chen ZQ, Tang YQ, Zhang Y, Jiang ZH, Mao EQ, Zou WG, Lei RQ, Han TQ,Zhang SD. Adenoviral transfer of human
, 百拇医药
interleukin-10 gene in lethalpancreatitis. World J Gastroenterol 2004;10:3021-3025
13 Sweeney KJ, Kell MR, Coates C, Murphy T, Reynolds JV. Serum antigen(s) drive the proinflammatory T cell
response in acute pancreatitis. BrJ Surg 2003;90:313-319
14 Uehara S, Gothoh K, Handa H, Tomita H, Tomita Y. Immune function inpatients with acute pancreatitis.
J Gastroenterol Hepatol 2003;18:363-370
, http://www.100md.com
15 张群华, 蔡端,吴树强,姜永峰,候兰娣, 张延龄. 急性坏死性胰腺炎大鼠的炎性递质变化和生长抑素的作用.
中华医学杂志 1997;77:355-358
16 Pezzilli R, Miniero R, Cappelletti O, Barakat B. Behavior of seruminterleukin 12 in human acute pancreatitis.
Pancreas 1999;18:247-251
17 艾迎春, 韩桂华, 郭公新,陈福军. IL -8和IL-12与急性胰腺炎分类的探讨.黑龙江医药科学 2004;27:34-35
18 姚婷, 王书奎, 陈军,姚堃, 秦浚川, 季晓辉.M-CSF、IL-10对单核细胞IL-12、IL-18产生及HLA-DR和CD80表达的影响.
细胞与分子免疫学杂志 2004;20:67-69
编辑 潘伯荣 审读 张海宁, 百拇医药( 赖铭裕, 梁志海, 唐国都, 孙学成, 邓德海)
